Not as simple as just punching a hole

Fivaz, Marc; Abrami, Laurence; Tsitrin, Yulia; Goot, F. Gisou van der

doi:10.1016/s0041-0101(01)00151-9

Cited by 43 publications

(33 citation statements)

References 75 publications

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“…Furthermore, RTX toxins also cause perturbations in cellular Ca 2+ levels that result, at least in part, from influx of extracellular Ca 2+ (Welch, 2001). Similarly, it has been proposed (but, to our knowledge, not yet proven) that Ca 2+ perturbations caused by aerolysin can trigger apoptosis (Nelson et al, 1999;Fivaz et al, 2001). Given the role for calmodulin and calpain in CPE action demonstrated in this report, it might be interesting to evaluate whether other pore-forming toxins can still activate apoptosis or oncosis pathways in the presence of calmodulin or calpain antagonists.…”

Section: +mentioning

confidence: 88%

The importance of calcium influx, calpain and calmodulin for the activation of CaCo-2 cell death pathways by Clostridium perfringens enterotoxin

Chakrabarti¹,

McClane²

2004

Cellular Microbiology

103

100

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SummaryCaCo-2 cells exhibit apoptosis when treated with low doses of Clostridium perfringens enterotoxin (CPE), but develop oncosis when treated with high CPE doses. This study reports that the presence of extracellular Ca 2+ in treatment buffers is important for normal activation of both those cell death pathways in CPE-treated CaCo-2 cells. Normal development of CPE-induced cell death pathway effects, such as morphologic damage, DNA fragmentation, caspase activation, mitochondrial membrane depolarization and cytochrome c release, was strongly inhibited when CaCo-2 cells were CPE-treated in Ca 2+ -free buffers. When treatment buffers contained Ca 2+ , CPE caused a rapid increase in CaCo-2 cell Ca 2+ levels, apparently because of increased Ca 2+ influx through a CPE pore. High CPE doses caused massive changes in cellular Ca 2+ levels that appear responsible for activating oncosis, whereas low CPE doses caused less perturbations in cellular Ca 2+ levels that appear responsible for activating apoptosis. Both CPE-induced apoptosis and oncosis were found to be calmodulin-and calpain-dependent processes. As Ca 2+ levels present in the intestinal lumen resemble those of Ca 2+ -containing treatment buffers used in this study, perturbations in cellular Ca 2+ levels and calpain/ calmodulin-dependent processes are also probably important for inducing enterocyte cell death during CPE-mediated gastrointestinal disease.

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Section: +mentioning

confidence: 88%

The importance of calcium influx, calpain and calmodulin for the activation of CaCo-2 cell death pathways by Clostridium perfringens enterotoxin

Chakrabarti¹,

McClane²

2004

Cellular Microbiology

103

100

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“…The cytotoxicity and heptamerization of aerolysin in T lymphocytes, however, are insensitive to MbCD treatment, thus arguing against the dependence of aerolysin heptamerization on DRMs (33). A plausible explanation for these apparently contradictory observations is that cholesterol depletion affects heptamerization in most cell types but not in T lymphocytes expressing unusually high levels of aerolysin receptors (10). Another likely explanation is that MbCD only affects cholesterol surrounding and outside of DRMs (9,29).…”

Section: Discussionmentioning

confidence: 99%

Clostridium perfringens ε-Toxin Forms a Heptameric Pore within the Detergent-insoluble Microdomains of Madin-Darby Canine Kidney Cells and Rat Synaptosomes

Miyata

Minami

Tamai

et al. 2002

Journal of Biological Chemistry

129

138

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Clostridium perfringens ⑀-toxin, which is responsible for enterotoxaemia in ungulates, forms a heptamer in rat synaptosomal and Madin-Darby canine kidney (MDCK) cell membranes, leading to membrane permealization. Thus, the toxin may target the detergent-resistant membrane domains (DRMs) of these membranes, in analogy to aerolysin, a heptameric pore-forming toxin that associates with DRMs. To test this idea, we examined the distribution of radiolabeled ⑀-toxin in DRM and detergent-soluble membrane fractions of MDCK cells and rat synaptosomal membranes. When MDCK cells and synaptosomal membranes were incubated with the toxin and then fractionated by cold Triton X-100 extraction and flotation on sucrose gradients, the heptameric toxin was detected almost exclusively in DRMs. The results of a toxin overlay assay revealed that the toxin preferentially bound to and heptamerized in the isolated DRMs. Furthermore, cholesterol depletion by methyl-␤-cyclodextrin abrogated their association and lowered the cytotoxicity of the toxin toward MDCK cells. When ⑀-protoxin, an inactive precursor able to bind to but unable to heptamerize in the membrane, was incubated with MDCK cell membranes, it was detected mainly in their DRMs. These results suggest that the toxin is concentrated and induced to heptamerize on binding to a putative receptor located preferentially in DRMs, with all steps from initial binding through pore formation completed within the same DRMs.

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“…[9][10][11][12] However, the involvement of such oligomers in cell death is not well understood because most toxin oligomer complexes themselves apparently do not punch holes in membrane and do not simply cause cell death by lysis. 13,14 Instead, the interaction of toxins with cells involves complicated pathways, the end result of which is cell death. [15][16][17] The Cry proteins of Bacillus thuringiensis (Bt) represent more than 100 phylogenetically related toxins with varied entomopathogenic activities.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of Bacillus thuringiensis Cry1Ab toxin depends on specific binding of the toxin to the cadherin receptor BT-R1 expressed in insect cells

et al. 2005

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The specific role of cadherin receptors in cytotoxicity involving Cry toxins of Bacillus thuringiensis and their interactions with cell membrane has not been defined. To elucidate the involvement of toxin-membrane and toxinreceptor interactions in cytotoxicity, we established a cellbased system utilizing High Five insect cells stably expressing BT-R 1 , the cadherin receptor for Cry1Ab toxin. Cry1Ab toxin is incorporated into cell membrane in both oligomeric and monomeric form. Monomeric toxin binds specifically to BT-R 1 whereas incorporation of oligomeric toxin is nonspecific and lipid dependent. Toxin oligomers in the cell membrane do not produce lytic pores and do not kill insect cells. Rather, cell death correlates with binding of the Cry1Ab toxin monomer to BT-R 1 , which apparently activates a Mg 2 þ -dependent cellular signaling pathway.

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Not as simple as just punching a hole

Cited by 43 publications

References 75 publications

The importance of calcium influx, calpain and calmodulin for the activation of CaCo-2 cell death pathways by Clostridium perfringens enterotoxin

The importance of calcium influx, calpain and calmodulin for the activation of CaCo-2 cell death pathways by Clostridium perfringens enterotoxin

Clostridium perfringens ε-Toxin Forms a Heptameric Pore within the Detergent-insoluble Microdomains of Madin-Darby Canine Kidney Cells and Rat Synaptosomes

Cytotoxicity of Bacillus thuringiensis Cry1Ab toxin depends on specific binding of the toxin to the cadherin receptor BT-R1 expressed in insect cells

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